The school was founded by the Franciscans in 1857, and from 1889 was administered by the Irish Christian Brothers. In 1999, St. Bon's became an independent Roman Catholic School in the Jesuit Tradition. In 2003, St. Bon's became a member of the Jesuit Secondary School Association.

In April 1857 the bishop laid the cornerstone of the college named after the Franciscan Order's most scholarly and famous theologian, St. Bonaventure. A year later, in March 1858, the new facilities opened. Dormitories were installed upstairs as the institution operated as a seminary. Seven years later in 1865 the college began to admit secular students and, in 1889, the Irish Christian Brothers assumed administrative responsibilities for the school.

The school was closed in 1998 due to the end of denominational education in the province. In 1999, the school was reopened with the Society of Jesus, from their local St. Pius X Church, offering administrative help; it is now the only K-12 private school, and the only Catholic school, in the city.

Some of Newfoundland's greatest political and cultural leaders were educated at St. Bon's. Among its graduates are many Rhodes scholars, Jubilee scholars, two lieutenant governors, three chief justices, five archbishops and six regular Bishops. In addition, Newfoundland prime ministersSir Edward Morris and Sir Michael Cashin were both St. Bon's alumni. Former premier of Newfoundland and Labrador, Danny Williams, also attended St. Bon's, although he graduated from nearby Gonzaga High School.

The school was also a perennial leader in sports and was the first educational institution to institute an annual sports day. The prestigious Boyle Trophy has a long association with the school.

The school is now well known for its excellence in music. Under the direction of Vincenza Etchegary, the school now has more than seven bands, has won numerous awards, and has traveled to MusicFest Canada to compete in competitions, winning several awards there. In 2004, St. Bonaventure's College Wind Ensemble won the CBC Radio 2004 Provincial School Band Competition for Newfoundland and Labrador. In 2007, the Wind Ensemble traveled to Orlando, Florida to compete in the All American Band Festival, and took home many awards, including Most Outstanding Band. The school's choirs have also achieved success in many local competitions under the direction of Kellie Walsh; the Senior Choir won the 2006 Kiwanis Rose Bowl, and the Treble Choir won the same award in 2007. In April 2009, the Wind Ensemble, Senior Jazz Band and the Treble Choir of the school travelled to Anaheim, California, to participate in the Heritage Music Festival, winning the top awards.